BACKGROUND: Clozapine has a range of serious adverse effects that may give rise to an increased risk of death. AIMS: To compare reasons for discontinuation of clozapine with reasons for discontinuation of risperidone long-acting injection in age-matched individuals treated in the same clinical environment. METHOD: Comparison of patients receiving clozapine and an age-matched control group receiving risperidone injection. RESULTS: We established outcome for 529 consecutive patients receiving clozapine and 250 receiving risperidone (161 discontinuers from each group were compared). Adverse effects (odds ratio OR=2.19, 95% CI 1.31-3.67) and death (OR=7.0, 95% CI 2.09-23.5) were more commonly observed as reasons for discontinuation of clozapine than of risperidone. Clozapine was less likely to be withdrawn because of ineffectiveness than was risperidone (OR=0.034, 95% CI 0.01-0.14). Standardised mortality ratio (SMR) was significantly raised for patients receiving clozapine (SMR=4.17, 95% CI 2.78-6.26). Pneumonia was the most common single cause of death. CONCLUSIONS: Clozapine use in patients with severe mental illness was associated with a significantly increased risk of death compared with that for the general population. Causation could not be established. Adverse effects and death are common causes of clozapine discontinuation.
BACKGROUND:Clozapine has a range of serious adverse effects that may give rise to an increased risk of death. AIMS: To compare reasons for discontinuation of clozapine with reasons for discontinuation of risperidone long-acting injection in age-matched individuals treated in the same clinical environment. METHOD: Comparison of patients receiving clozapine and an age-matched control group receiving risperidone injection. RESULTS: We established outcome for 529 consecutive patients receiving clozapine and 250 receiving risperidone (161 discontinuers from each group were compared). Adverse effects (odds ratio OR=2.19, 95% CI 1.31-3.67) and death (OR=7.0, 95% CI 2.09-23.5) were more commonly observed as reasons for discontinuation of clozapine than of risperidone. Clozapine was less likely to be withdrawn because of ineffectiveness than was risperidone (OR=0.034, 95% CI 0.01-0.14). Standardised mortality ratio (SMR) was significantly raised for patients receiving clozapine (SMR=4.17, 95% CI 2.78-6.26). Pneumonia was the most common single cause of death. CONCLUSIONS:Clozapine use in patients with severe mental illness was associated with a significantly increased risk of death compared with that for the general population. Causation could not be established. Adverse effects and death are common causes of clozapine discontinuation.
Authors: W H Man; A Pérez-Pitarch; I Wilting; E R Heerdink; W W van Solinge; A C G Egberts; A D R Huitema Journal: Br J Clin Pharmacol Date: 2018-04-02 Impact factor: 4.335
Authors: John Lally; Jennifer Brook; Thomas Dixon; Fiona Gaughran; Sukhi Shergill; Narbeh Melikian; James H MacCabe Journal: Ther Adv Psychopharmacol Date: 2014-06